Study of the association of adrenomedullin and basic-fibroblast growth factors with the peripheral arterial blood flow and endothelial dysfunction biomarkers in type 2 diabetic patients with peripheral vascular insufficiency.

BACKGROUND: Progressive micro-vascular vaso-degeneration is the major factor in progression of diabetic complications. Adrenomedullin (AM) and basic-Fibroblast growth factor (b-FGF) are strongly correlated with angiogenesis in vascular diseases. This study aims to provide base line data regarding the vascular effects and correlation of AM, and b-FGF with the peripheral blood flow in diabetic patients with peripheral vascular disease (PVD), and their effect on endothelial dysfunction markers. Ninety age- and sex matched females were enrolled in the study: 30 were controls, 30 had diabetes without complications (group II) and 30 had diabetes with PVD (group III) diagnosed by ankle/ brachial index (A/BI). Plasma levels of AM, b-FGF, intercellular adhesion molecule -1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by indirect enzyme immunoassay (ELISA). RESULTS: There was a significant increase in plasma AM, VCAM-1and ICAM-1, while a significant decrease in plasma b-FGF in diabetic patients with PVD (p < 0.05). A positive correlation was observed between plasma AM, b-FGF and A/BI and a negative correlation with VCAM -1 and ICAM in diabetic PVD. AM was not a predictor, while b-FG, VCAM-1 and ICAM-1 could be predictors for peripheral blood flow in diabetic PVD. CONCLUSION: This study elucidates for the first time that AM and b-FGF are correlated and have a direct impact on the peripheral blood flow, the rise of AM in diabetic PVD may be a consecutive and compensatory vasculo-protective effect as its angiogenic and anti-inflammatory properties act to relief the endothelial insult. Down expression of b-FGF may be a predisposing factor for micro-vascular derangement. It is not clear if the rise of AM and the decline of b- FGF levels may be consequences or predisposing factors for VCAM-1 and ICAM-1 elevation as these endothelial dysfunction biomarkers could reduce peripheral blood flow and vascular integrity. It is optimistic to believe that drug intervention through AM and b-FGF administration together with reversing the endothelial inflammatory process by targeting VCAM and ICAM could reduce the prevalence of diabetic vascular complications, reduce the risk of cerebrovascular and cardiovascular morbidity in diabetes through normalizing vascular endothelium function and peripheral blood flow.

Evaluation of plasma soluble fatty acid synthase levels among Saudi autistic children. Relation to disease severity.

OBJECTIVE: To investigate the role of an apoptotic marker soluble fatty acid synthase (s-Fas) antigen in children with autism and its correlation to disease severity. METHODS: The study was conducted between May 2011 and April 2012 at the Department of Physiology and Autism Research and Treatment Center (ARTC) at King Khalid University Hospital and King Saud University (KSU) in Riyadh, Kingdom of Saudi Arabia. Sixty children were enrolled, 20 as controls, 20 mild, and 20 with severe autism. Plasma samples were analyzed for s-Fas. RESULTS: The levels of s-Fas were significantly higher in autistic children compared with control children (p<0.05). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with mild autism, and there was a positive correlation between s-Fas levels and severe autism (p<0.05). CONCLUSION: The s-Fas level is high in Saudi children with severe autism, and can be considered an indicator of disease severity. These findings may offer a new therapeutic or diagnostic tool for children suffering from severe autism.

Evaluation of plasma levels of adrenomedullin and ghrelin, and their correlation with electrophysiological changes in diabetic neuropathy.

OBJECTIVE: To evaluate plasma levels of adrenomedullin (AM) and ghrelin and their correlation with the electrophysiological changes in diabetic neuropathy. METHODS: The current study was conducted from March 2008 to November 2010 at the Clinical Physiology Department, King Abdulaziz University Hospital, King Saud University, Riyadh, Kingdom of Saudi Arabia on 90 females divided into 30 controls (group I), 30 controlled diabetic patients (group II), and 30 with peripheral neuropathy (group III). All electrophysiological and biochemical measurements of AM and ghrelin were investigated. RESULTS: There was a significant decrease of motor and sensory nerve conduction velocity and prolongation of F wave response of median, ulnar, peroneal, and sural nerves in diabetic patients with neuropathy. Ankle/brachial index (A/BI) showed insignificant change in all groups compared with the control group. There was significant decrease of plasma levels of AM and ghrelin in group III compared with group I. The results revealed that AM and ghrelin were positively correlated with peripheral nerves motor and sensory conduction velocities. CONCLUSION: The altered concentration of AM and ghrelin in diabetic neuropathy could indicate a pathophysiological role. The decline of plasma levels of AM and ghrelin in diabetic neuropathy may be a causative factor, they have neuroprotective and vasculoprotective effects, so their lack could induce neuronal injury and advancement of neuropathy, but the precise role of AM and ghrelin in the pathogenesis of diabetic neuropathy is still to be elucidated.

Study of dual angiogenic/neurogenic growth factors among Saudi autistic children and their correlation with the severity of this disorder.

OBJECTIVE: To investigate the role of 2 angiogenic/neurogenic growth factors, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) in Saudi children with autism. METHODS: The study included a total of 60 children that included 20 controls and 40 patients with a confirmed diagnosis of autism. The study was conducted in the Department of Physiology, Faculty of Medicine, King Saud University, and in the Autism Research and Treatment Center, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between May 2010 and April 2011. Collected blood plasma samples were analyzed for VEGF and PDGF. RESULTS: The levels of VEGF showed a non-significant change in autistic children compared with the control children (p=0.065). The levels of PDGF were significantly higher in autistic children compared with the control children (p=0.01). Furthermore, this increase was significantly more pronounced in children with severe autism as compared with children with mild autism (p=0.001), and it was not correlated to the severity of the disorder. CONCLUSION: A rise in PDGF may contribute to the pathophysiology of the disorder, either alone or in synergy with other neurotrophic factors to induce an angiogenic-neuroprotective effect. Plasma VEGF has no causative or compensatory contribution to the pathology of this disorder.

Electrophysiological changes, plasma vascular endothelial growth factor, fatty acid synthase, and adhesion molecules in diabetic neuropathy.

OBJECTIVE: To evaluate the electrophysiological changes, blood flow index, vascular endothelial growth factor (VEGF), soluble fatty acid synthase (s-FAS), and intercellular adhesion molecule (I-CAM) in diabetic neuropathy. METHODS: This study was conducted from March 2004 to November 2007 on 60 type II diabetic patients and 30 controls, recruited from the Diabetic Research Center of King Abdul-Aziz University Hospital, Riyadh, Kingdom of Saudi Arabia. Electrophysiological studies were carried out in the Clinical Physiology Laboratory. Patients and controls were of the same age, gender, and weight. RESULTS: The study included 30 controls (group I), 30 diabetics type II without complications (group II), and 30 with peripheral neuropathy (group III). There was a significant decrease of motor conduction velocity, prolongation of F wave response of median, ulnar, peroneal nerves, significant decrease of median and ulnar sensory conduction velocity, sural nerve conduction velocity and sensory amplitude, showed significant decrease, ankle/brachial index (A/BI) showed insignificant change, also there was a significant increase of plasma VEGF, s-FAS, and ICAM all in group III compared to groups I and II. The results revealed that VEGF and s-FAS are good predictors for median nerve motor conduction velocity, also VEGF is a good predictor of sural nerve sensory conduction velocity in diabetic neuropathy. CONCLUSION: The rise of VEGF in diabetic neuropathy may be protective to preserve the nerve blood flow, the significant rise of s-FAS may be causative in advancement of neuropathy, I-CAM high levels suggest its leading role in interaction between endothelium, blood elements, and peripheral nerves. The results showed that human neuropathy is the result of multiple factors, thus, it may be optimistic to believe that reversing one of them, such as s-FAS will halt, or reverse nerve damage. Targeting multiple mechanisms simultaneously, by administering combination treatments of VEGF, and anti-apoptotic drugs may be prospective.